Arrhythmias In Brugada Syndrome Research Articles

Temperature and ST-segment morphology remote monitoring: new perspectives for implantable cardiac monitors in Brugada syndrome.

Patients with Brugada syndrome (BrS) face an increased risk of ventricular arrhythmias and sudden cardiac death. Implantable cardiac monitors (ICMs) have emerged as effective tools for detecting arrhythmias in BrS. Technological advancements, including temperature sensors and improved subcutaneous electrocardiogram (subECG) signal quality, hold promise for further enhancing their utility in this population. We present a case of a 40-year-old man exhibiting a BrS type 2 pattern on 12-lead ECG, who underwent ICM insertion (BIOMONITOR IIIm, BIOTRONIK) due to drug-induced BrS type 1 pattern and a history of syncope, with a negative response to programmed ventricular stimulation. The device contains an integrated temperature sensor and can transmit daily vital data, such as mean heart rate and physical activity. Several months later, remote alerts indicated a temperature increase, along with transmitted subECGs suggesting a fever-induced BrS type 1 pattern. The patient was promptly advised to commence antipyretic therapy. Over the following days, remotely monitored parameters showed decreases in mean temperature, physical activity, and mean heart rate, without further recurrence of abnormal subECGs. ICMs offer valuable insights beyond arrhythmia detection in BrS. Early detection of fever using embedded temperature sensors may improve patient management, while continuous subECG morphological analysis has the potential to enhance risk stratification in BrS patients.

Demonstration of Arrhythmia Substrate-Associated Dispersion of Repolarization by Epicardial Unipolar Mapping in Brugada Syndrome

BackgroundEpicardial unipolar mapping has not been thoroughly investigated in Brugada syndrome (BrS). ObjectivesThis study aims to examine the characteristics of epicardial unipolar potentials in BrS and investigate the differences from overt cardiomyopathy. MethodsEpicardial mapping was performed in 8 patients with BrS and 6 patients with cardiomyopathy. We investigated the J-wave amplitudes using unipolar recordings at delayed potential (DP) sites via bipolar recordings. The repolarization time (RT) at and around the DP recording sites was measured, and maximum dispersion of the RT divided by the distance was defined as the RT dispersion index. ResultsEpicardial mapping at baseline revealed significantly higher J-wave amplitude with bipolar DP in patients with BrS than in patients with cardiomyopathy. J-wave amplitude ≥0.42 mV had 99.1% sensitivity and 100% specificity for diagnosing BrS. The RT dispersion index was significantly higher in patients with BrS than in patients with cardiomyopathy at baseline. In all patients with BrS, coved-type unipolar electrograms without negative T waves (short RT) appeared close to coved-type electrograms with negative T waves (long RT) at the DP recording sites after pilsicainide administration. Thus, a steep RT dispersion was observed in this region, and ventricular arrhythmias emerged from this shorter RT area in all 3 patients with BrS in whom ventricular arrhythmias were induced. ConclusionsBipolar DP-related prominent unipolar J waves and steep repolarization gradients may be more specific for characterizing BrS than for overt cardiomyopathy. Ventricular arrhythmias in BrS are associated with a steep repolarization gradient, indicating phase 2 re-entry as a possible cause.

SCN5A gene variants and arrhythmic risk in Brugada syndrome: An updated systematic review and meta-analysis

BackgroundA rare gene variant in SCN5A can be found in approximately 20%–25% of patients with Brugada syndrome (BrS). ObjectiveThe aim of this systematic review and meta-analysis was to evaluate the differences in clinical characteristics of BrS patients with and without SCN5A rare variants and the prognostic role of SCN5A for ventricular arrhythmias in BrS. MethodsPubMed and Cochrane Central Register of Controlled Trials (CENTRAL) were systematically searched from inception to January 2024 to identify all relevant studies. Studies were analyzed if they included patients diagnosed with BrS in whom genetic testing for SCN5A variants was performed and arrhythmic outcomes were reported. ResultsA total of 17 studies with 3568 BrS patients, of whom 3030 underwent genetic testing for SCN5A variants, fulfilled the eligibility criteria and were included. Compared with SCN5A− patients, SCN5A+ BrS patients more frequently had spontaneous type 1 electrocardiogram, history of syncope, and documented arrhythmias. Furthermore, higher PQ and QRS intervals in SCN5A+ BrS patients compared with SCN5A− have been found. The pooled analysis demonstrated a significant association between the presence of SCN5A rare variants in BrS patients and the risk of major arrhythmic events, with a pooled odds ratio of 2.14 (95% confidence interval, 1.53–2.99; I2 = 29%). ConclusionSCN5A+ BrS patients showed a worse clinical phenotype compared with SCN5A−. The pooled analysis demonstrated a significant association between SCN5A+ mutation status and the risk of major arrhythmic events in BrS patients.

Brugada Syndrome: A Comprehensive Review of Fundamental and Electrophysiological New Findings.

Brugada syndrome is characterized by pronounced J-ST segment elevation in the right precordial leads on surface electrocardiograms. The etiological underpinnings of these distinctive features have been the subject of extensive debate, encompassing various theories related to repolarization anomalies and conduction irregularities. Genetic investigations have unveiled SCN5A, the gene encoding NaV1.5, a critical sodium channel, as the most frequently implicated causative gene, with mutations typically manifesting as loss of function. Nonetheless, the detection rate of SCN5A mutations remains below 20%, underscoring the intricate genetic landscape of the syndrome. Histological analyses have divulged localized structural irregularities, primarily marked by fibrotic alterations, within the right ventricular outflow tract. Electrophysiological inquiries employing direct epicardial mapping techniques have uncovered localized conduction impediments concomitant with modifications in unipolar morphologies within the J-ST segment. Thus, the theory positing conduction abnormalities emerges as a compelling mechanism accounting for J-ST segment elevation. However, the precise mechanisms governing the onset of life-threatening tachyarrhythmias remain shrouded in uncertainty. Recent clinical case reports have proffered evidence supporting the notion that phase 2 reentry, arising from the marked heterogeneity in action potentials within the epicardial domain, may serve as the instigator of premature ventricular contractions, ultimately culminating in ventricular fibrillation. In light of these developments, it becomes increasingly evident that comprehending the mechanisms underlying the electrocardiographic manifestations and lethal arrhythmias in Brugada syndrome necessitates the consideration of a multifaceted perspective, transcending the binary discourse of repolarization versus depolarization anomalies.

Unmasking a Silent Killer and Understanding Sudden Cardiac Death in Brugada Syndrome: A Traditional Review.

Brugada syndrome (BrS) is an intricate and heterogeneous genetic disorder that engenders a formidable risk of life-threatening ventricular arrhythmias (VAs). While initially regarded as an electrophysiological aberration, emergent studies have illuminated the presence of underlying structural anomalies in select BrS cases. Although mutations in the SCN5A gene encoding the α-subunit of the cardiac sodium channel were originally identified as a primary causative factor; they account for only a fraction of the syndrome's multifaceted complexity pointing at genetic heterogeneity as a contributing factor. Remarkably, BrS has been linked to a higher incidence of fatal arrhythmic incidents and sudden cardiac death (SCD) with about 4% of SCD cases thought to be caused by BrS. Patients who spontaneously exhibit type one Brugada ECGs are more likely to experience cardiac events,emphasizing the importance of early risk stratification. To aid in risk stratification, the Shanghai score; a multifactorial risk stratification scoring system that incorporates ECG, clinical history, family history, and genetic test results; is utilized to identify those most susceptible to SCD. Beyond single ECGs, evaluation of arrhythmic findings from 24-hour Holter monitoring, ECG variables, electrophysiologic study (EPS) status in the temporal domain, and EPS data collected over time are all critical factors in risk classification. Among management options avoidance of triggers, early risk stratification, and implantation of an Implantable Cardioverter-Defibrillator (ICD) are recommended for asymptomatic patients. For symptomatic patients, pharmacotherapy and ICD implantation are available, with the latter being a highly effective choice for treating and preventing lethal arrhythmias in BrS.

Risk stratification of severe ventricular arrhythmias in Brugada syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Background Predicting likelihood of severe ventricular arrhythmias in Brugada syndrome (BrS) patients is challenging due to conflicting evidence. Objectives The goal of this study was to construct a prediction model of severe ventricular arrhythmias (VAs) for BrS patients. Methods Two hundred forty-two BrS patients were enrolled from 2008 to 2019 in a single-center cohort study. Those patients were followed up until December 2021. Clinical data and multiple ECG markers were collected and analyzed to determine the risk factors of severe VAs and sudden cardiac death (SCD). Multivariate logistic regression analysis was then used to develop a risk prediction model for adverse arrhythmic outcomes in BrS patients. Results During the follow-up (90.1 ± 45.8 months) of 242 BrS patients (mean age 42.3 ± 12 years; 94.6% male), 49 (20.2%) patients had syncope/pre-syncope due to VAs and 7 (2.9%) patients had aborted cardiac arrest. In multivariable analysis, epsilon wave, early repolarization sign, S wave duration in lead I, QRS duration in V2 and Tp-e duration were significant associated with adverse arrhythmic outcomes. A clinical model including these five significant predictors had a good performance to predict outcomes with balanced accuracy of 0.86 and area under curve of 0.93 (95% CI, 0.89-0.96, p < 0.001) indicating a good discriminative ability. Furthermore, the Hosmer–Lemeshow test and the calibration plot showed a good fit between the predicted and observed probabilities of the predictive model. Conclusions This study constructed a risk prediction model for severe VAs in BrS patients with a high predictive accuracy.

Role of subcutaneous implantable loop recorder for the diagnosis of arrhythmias in Brugada syndrome: A United Kingdom single-center experience.

Experience with implantable loop recorders (ILRs) in Brugada syndrome (BrS) is limited. The purpose of this study was to evaluate the indications and yield of ILR monitoring in a single-center BrS registry. Demographic, clinical and follow-up data of BrS patients with ILR were collected. Of 415 BrS patients recruited consecutively, 50 (12%) received an ILR (58% male). Mean age at ILR implantation was 44 ± 15 years. Thirty-one (62%) had experienced syncopal or presyncopal episodes, and 23 (46%) had palpitations. During median follow-up of 28 months (range 1-68), actionable events were detected in 11 subjects (22%); 7 had recurrences of syncope/presyncope, with 4 showing defects in sinus node function or atrioventricular conduction. New supraventricular tachyarrhythmias were recorded in 6 subjects; a run of fast nonsustained ventricular tachycardia was detected in 1 patient. Patients implanted with an ILR were less likely to show a spontaneous type 1 pattern or depolarization electrocardiographic (ECG) abnormalities compared to those receiving a primary prevention implantable-cardioverter defibrillator. Age at implantation, gender, Shanghai score, and ECG parameters did not differ betweensubjects with and those without actionable events. ILR-relatedcomplications occurred in 3 cases (6%). In a large cohort of BrS patients, continuous ILR monitoring yielded a diagnosis of tachy- or bradyarrhythmic episodes in 22% of cases. Recurrences of syncope were associated with bradyarrhythmic events. Use of ILR can be helpful in guiding the management of low-/intermediate-risk BrS patients and ascertaining the cause of unexplained syncope.

The clinical utility of procainamide-induced late potentials on the signal averaged ECG.

Late potentials (LPs) identified on the signal averaged electrocardiogram (SAECG) are a marker for an increased risk of arrhythmias in Brugada syndrome (BrS). Procainamide is a sodium channel blocker used to diagnose BrS. The effects of Procainamide on the SAECG in those with BrS and the significance of Procainamide-induced LPs are unknown. Procainamide provocation was performed for suspected BrS with 12-lead and SAECG pre- and post-infusion. Filtered QRS duration (fQRSd), duration of low amplitude signals<40 μV (LAS40) and root-mean-square voltage in the terminal 40ms (RMS40) were determined. Data from 150 patients were included in the analysis (mean age 44.5 years, 109 males). Procainamide increased fQRSd (Pre 118.8±10.5ms, post 121.2±10.2ms, p<0.001) and LAS40 (Pre 38.7±9.8ms, post 40.2±10.5ms, p=0.005) and decreased RMS40 (Pre 24.6±12ms, post 22.8±12ms, p=0.002). LPs were present in 68/150 (45%) at baseline. Fifteen patients with negative baseline SAECGs had LPs unmasked by Procainamide, but six patients had LPs at baseline that were no longer present following Procainamide. Comparing those with normal hearts (n=48) to those with a final diagnosis of BrS (n=38), Procainamide prolonged fQRSd to a greater extent in those with BrS. Comparing those with Procainamide-induced LPs to those with no LPs at any time did not highlight any aspect of phenotype and did not correlate with a history of ventricular arrhythmias. Procainamide influences the SAECG, provoking LPs in a small proportion of patients. However, there is no evidence that Procainamide-induced LPs provide additional diagnostic information or aid risk stratification.

Specific decreasing of Na+ channel expression on the lateral membrane of cardiomyocytes causes fatal arrhythmias in Brugada syndrome

Reduced cardiac sodium (Na+) channel current (INa) resulting from the loss-of-function of Na+ channel is a major cause of lethal arrhythmias in Brugada syndrome (BrS). Inspired by previous experimental studies which showed that in heart diseases INa was reduced along with expression changes in Na+ channel within myocytes, we hypothesized that the local decrease in INa caused by the alteration in Na+ channel expression in myocytes leads to the occurrence of phase-2 reentry, the major triggering mechanism of lethal arrhythmias in BrS. We constructed in silico human ventricular myocardial strand and ring models, and examined whether the Na+ channel expression changes in each myocyte cause the phase-2 reentry in BrS. Reducing Na+ channel expression in the lateral membrane of each myocyte caused not only the notch-and-dome but also loss-of-dome type action potentials and slowed conduction, both of which are typically observed in BrS patients. Furthermore, the selective reduction in Na+ channels on the lateral membrane of each myocyte together with spatial tissue heterogeneity of Na+ channel expression caused the phase-2 reentry and phase-2 reentry-mediated reentrant arrhythmias. Our data suggest that the BrS phenotype is strongly influenced by expression abnormalities as well as genetic abnormalities of Na+ channels.

Spatial QRS-T angle: A new risk marker for sudden cardiac arrest in Brugada syndrome?

Ventricular arrhythmias in Brugada syndrome (BrS) may be due to a combination of myocardial depolarization and repolarization abnormalities. The spatial QRS-T angle, measured by 3D ECG, reflects both myocardial depolarization and repolarization and has been proposed as a marker for sudden cardiac death risk in several cardiomyopathies. This marker has never been evaluated in BrS patients. To evaluate the prognostic significance of the spatial QRS-T angle in patients with a spontaneous Brugada type 1 pattern (SBT1). 8 patients with a SBT1 were included (8 males, mean age 49.1 ± 10.9 years-old), 4 experienced sudden cardiac arrest or documented ventricular fibrillation (SCA/VF) at mean age of 38.8 ± 14.3 years-old. We analyzed conventional ECG and 3D ECG data using the CAVIAR method and compared data from VF/SCA group to other subjects. The spatial angle between the onset of the QRS and the T-wave loop (ODIR angle) was significantly higher in the SCA/VF group (49.1 ± 26.0 vs. 19.8 ± 3.8, P = 0.029). There was no significant difference between patients for conventional ECG measurements (PR interval 187.0 ± 29.6 ms in the SCA/VF group vs. 186.0 ± 38.7 ms, P = 1, QRS duration 130.0 ± 38.7 ms vs. 106.5 ± 12.5 ms, P = 0.30, corrected QT interval 471.8 ± 8.4 ms vs. 404.3 ± 45.1 ms, P = 0.057, Tpeak–Tend interval 115.5 ± 3.8 ms vs. 107.5 ± 34.7 ms, P = 1) ( Fig. 1 ). The spatial angle between the onset of QRS and the T-wave loop appears to be significantly correlated with the risk of VF/SCD in BrS patients. A prospective study is needed to confirm these findings.

Heart rate differences between symptomatic and asymptomatic Brugada syndrome patients at night

Objective: Ventricular arrhythmias in Brugada syndrome (BS) mainly occur at rest, especially during nighttime, suggesting that parasympathetic activity at night may play an important role in the arrhythmogenesis of the disease. This study examined and compared the autonomic function of symptomatic and asymptomatic BS patients overnight. Approach: We analyzed various heart rate variability (HRV) and heart rate complexity (HRC) markers in a clinical series including 87 BS patients, where 23 were symptomatic. Main results: Statistically significant differences were found in markers MIRR, SDNN, SDANN, and SampEn, suggesting that symptomatic patients may be related to lower heart rate variability and complexity values, as well as to greater circadian fluctuations overnight. Significance: The results provide further evidence for the role of autonomic imbalance in the pathophysiology of BS, highlighting the relevance of nighttime analysis to the unmasking of significant ANS changes. Based on these outcomes, the role of HRV and HRC assessment at night could be a step forward towards the understanding of BS and the risk for the occurrence of symptoms in these patients, with a potential future impact on therapeutic strategies.

Multivariate classification of Brugada syndrome patients based on autonomic response to exercise testing.

Ventricular arrhythmias in Brugada syndrome (BS) typically occur at rest and especially during sleep, suggesting that changes in the autonomic modulation may play an important role in arrhythmogenesis. The autonomic response to exercise and subsequent recovery was evaluated on 105 patients diagnosed with BS (twenty-four were symptomatic), by means of a time-frequency heart rate variability (HRV) analysis, so as to propose a novel predictive model capable of distinguishing symptomatic and asymptomatic BS populations. During incremental exercise, symptomatic patients showed higher HFnu values, probably related to an increased parasympathetic modulation, with respect to asymptomatic subjects. In addition, those extracted HRV features best distinguishing between populations were selected using a two-step feature selection approach, so as to build a linear discriminant analysis (LDA) classifier. The final features subset included one third of the total amount of extracted autonomic markers, mostly acquired during incremental exercise and active recovery, thus evidencing the relevance of these test segments in BS patients classification. The derived predictive model showed an improved performance with respect to previous works in the field (AUC = 0.92 ± 0.01; Se = 0.91 ± 0.06; Sp = 0.90 ± 0.05). Therefore, based on these findings, some of the analyzed HRV markers and the proposed model could be useful for risk stratification in Brugada syndrome.

Pharmacological Therapy in Brugada Syndrome

Brugada syndrome (BrS) is a cardiac disease caused by an inherited ion channelopathy associated with a propensity to develop ventricular fibrillation. Implantable cardioverter defibrillator implantation is recommended in BrS, based on the clinical presentation in the presence of diagnostic ECG criteria. Implantable cardioverter defibrillator implantation is not always indicated or sufficient in BrS, and is associated with a high device complication rate. Pharmacological therapy aimed at rebalancing the membrane action potential can prevent arrhythmogenesis in BrS. Quinidine, a class 1A antiarrhythmic drug with significant Ito blocking properties, is the most extensively used drug for the prevention of arrhythmias in BrS. The present review provides contemporary data gathered on all drugs effective in the therapy of BrS, and on ineffective or contraindicated antiarrhythmic drugs.

Insertion of an ICD for Brugada syndrome

Brugada syndrome is an inherited heart condition that affects the electrophysiology in the structurally normal heart. As a result of this, it can cause ventricular arrhythmias. Diagnosis is not always straightforward and cannot always be recognised on an electrocardiogram. Patients will undergo investigations for diagnosis and analysis of their risk of ventricular arrhythmias. The results will lead to appropriate treatment recommendations. The present article will critically analyse current research and guidelines used for the risk stratification of ventricular arrhythmias in Brugada syndrome. Alongside this, there is a case study of a 60-year-old man with an incidental finding of Brugada syndrome that was asymptomatic. The case study discusses the psychosocial issues surrounding ICD insertion and diagnosis of a sudden cardiac death syndrome. The need for an international registry to understand the syndrome is necessary. In the meantime, educating patients about risk-reducing lifestyle choices is important.

Heart rate complexity analysis in Brugada syndrome during physical stress testing

Symptoms such as ventricular arrhythmias in Brugada syndrome (BS) typically occur at rest, especially during sleep, suggesting that the autonomic nervous system (ANS) function may be relevant in the arrhythmogenesis of the disease. The aim of this work was to assess the ANS response captured by nonlinear heart rate variability (HRV) measures in 69 patients diagnosed with BS, who underwent a standardized physical stress test. Heart rate complexity (HRC) was evaluated by the power-law scaling analysis (β slope) during rest, exercise, recovery and rest post-recovery, in order to discriminate between symptomatic and asymptomatic BS patients. Symptomatic patients showed a significant reduction in HRC in comparison to asymptomatic subjects, after exertion (p = 0.015); during the whole recovery period (p = 0.023), and in particular within the passive recovery phase (p = 0.025), as well as during rest post-recovery (p = 0.022). Based on these results, symptoms could be associated with a lower ANS complexity during the stress test stages where parasympathetic activity is predominant. Therefore, the proposed HRV indicators could be of help in the risk stratification of asymptomatic patients.

A Case Report on Brugada Syndrome and Anesthesia Considerations

Brugada Syndrome (BrS) is a rare autosomal disease caused by a genetic mutation affecting the ion channels of the cardiac conduction system. The administration of some routinely used anesthetic agents have shown to trigger spontaneous ventricular arrhythmias on BrS patients leading to sudden cardiac arrest. This is a case report on a 20year-old male patient with a history of cocaine abuse presenting to the emergency room (ER) with palpitations, chest discomfort, and syncope. Electrocardiogram (ECG) changes led to the diagnosis of BrS. The patient underwent an automatic implantable cardioverterdefibrillator (AICD) under general anesthesia without any complications, however routine anesthetic agents may induce lethal arrhythmias in BrS. This case report focuses on increasing the safety awareness for anesthesia care of patients with BrS.

EP News: Basic and Translational

Electrocardiographic changes and arrhythmias in Brugada syndrome (BrS) remain controversial. Mutations in the Na channel gene SCN5A and its regulatory proteins have been linked to BrS. Aiba et al (Circ Cardiovasc Genet 2014;7:249, PMID 24795344) studied the properties of a BrS SCN5A mutation of a protein kinase A (PKA) consensus phosphorylation site, R526H. In vitro PKA phosphorylation was detected in the I-II linker of wild-type (WT) Na channels, but not in R526H or S528A mutants. Surface expression and peak Na current (INa) densities of R526H and S528A channels were reduced as compared with WT channels. Infection of rat cultures with WT and mutant channels increased conduction velocity compared with controls, but PKA stimulation significantly increased peak INa and conduction velocity only in WT cultures. With the intracellular application of NADH, both WT and mutant INa decrease, but this effect is reversed by PKA stimulation in WT channels but not in mutant channels. The authors conclude that the BrS mutation R526H is associated with a reduction in basal INa and a failure of PKA stimulation to augment the current, thus predisposing to arrhythmias in patients with BrS.

A mutation causing Brugada syndrome identifies a mechanism for altered autonomic and oxidant regulation of cardiac sodium currents.

The mechanisms of the electrocardiographic changes and arrhythmias in Brugada syndrome (BrS) remain controversial. Mutations in the sodium channel gene, SCN5A, and regulatory proteins that reduce or eliminate sodium current (INa) have been linked to BrS. We studied the properties of a BrS-associated SCN5A mutation in a protein kinase A (PKA) consensus phosphorylation site, R526H. In vitro PKA phosphorylation was detected in the I-II linker peptide of wild-type (WT) channels but not R526H or S528A (phosphorylation site) mutants. Cell surface expression of R526H and S528A channels was reduced compared with WT. Whole-cell INa through all channel variants revealed no significant differences in the steady-state activation, inactivation, and recovery from inactivation. Peak current densities of the mutants were significantly reduced compared with WT. Infection of 2D cultures of neonatal rat ventricular myocytes with WT and mutant channels increased conduction velocity compared with noninfected cells. PKA stimulation significantly increased peak INa and conduction velocity of WT but not mutant channels. Oxidant stress inhibits cardiac INa; WT and mutant INa decreases with the intracellular application of reduced nicotinamide adenine dinucleotide (NADH), an effect that is reversed by PKA stimulation in WT but not in R526H or S528A channels. We identified a family with BrS and an SCN5A mutation in a PKA consensus phosphorylation site. The BrS mutation R526H is associated with a reduction in the basal level of INa and a failure of PKA stimulation to augment the current that may contribute to the predisposition to arrhythmias in patients with BrS, independent of the precipitants.

Acidosis: A Possible Trigger for Brugada Syndrome Associated Arrhythmia

Brugada Syndrome (BrS) is an inherited cardiac arrhythmia implicated in SIDS and sudden death in young men. BrS is caused by loss-of-function mutations in the cardiac voltage-gated sodium channel NaV1.5. The decrease in sodium current can lead to electrical abnormalities in the ventricular action potential that can degenerate into ventricular tachycardia. The ECG phenotype and electrical abnormalities associated with BrS are not always present and are often unmasked clinically with sodium channel blockers. Paradoxically, BrS associated arrhythmias manifest during and after exercise as well as in sleeping infants. We hypothesize that one trigger for arrhythmias in BrS may be extracellular acidosis, which can occur during both exercise and sleep apnea. We used whole-cell patch clamp to characterize 3 BrS mutants, R376H, R1193Q, and E1784K, at pH 7.4 and pH 6.0. At pH 7.4 all mutants have reduced current compared to WT channels and there are changes in channel activation and fast inactivation. At pH 6.0, E1784K showed the largest proton-dependent effect with a 20 mV depolarizing shift in the midpoint voltage of activation compared to the 12 mV shift in WT. All 3 mutants showed decreased function at pH 6.0 although the magnitude of the shifts was not always different from WT. Overall, extracellular acidosis would be expected to challenge already decreased sodium currents, particularly in the E1784K mutant. Therefore, acidosis may be one of the triggers for arrhythmia in BrS patients.

Fever and the electrocardiogram: What about Brugada syndrome?

In 2000, colleagues from Spain appreciated that fever could evoke malignant arrhythmias in Brugada syndrome and in the years thereafter many more examples have been reported.1–5 Brugada syndrome is an inheritable arrhythmia syndrome associated with a characteristic electrocardiogram (ECG; type-1 or coved-type Brugada ECG). The pathophysiological mechanisms underlying Brugada syndrome are not yet resolved but may include depolarization or repolarization abnormalities.6 Although most patients with Brugada syndrome will not have arrhythmias during follow-up, some patients are extremely symptomatic and may die suddenly or have repetitive malignant ventricular arrhythmias.